What is the recommended treatment regimen for a patient with Pulmonary Tuberculosis (PTB) and Acid-Fast Bacilli (AFB) positive sputum?

Treatment Regimen for Pulmonary Tuberculosis with AFB Positive Sputum

For patients with pulmonary tuberculosis (PTB) and positive acid-fast bacilli (AFB) sputum, the recommended treatment is a four-drug regimen of isoniazid, rifampin, pyrazinamide, and ethambutol for the initial 2 months, followed by isoniazid and rifampin for 4 months, for a total treatment duration of 6 months. 1, 2

Initial Phase (First 2 Months)

• A four-drug regimen consisting of isoniazid, rifampin, pyrazinamide, and ethambutol should be initiated promptly when AFB smears are positive, as this provides strong inferential evidence for TB diagnosis 3
• Recommended dosages for adults:
  • Isoniazid: 5 mg/kg (up to 300 mg) daily 4
  • Rifampin: 10 mg/kg (up to 600 mg) daily 2
  • Pyrazinamide: 15-30 mg/kg daily (see weight-based dosing table below) 3
  • Ethambutol: 15-20 mg/kg daily 3
• The initial phase medications may be administered:
  • Daily for the full 2 months (preferred approach) 1
  • Daily for 2 weeks followed by twice weekly administration for 6 weeks 1
  • Three times weekly throughout the initial phase 1

Continuation Phase (Next 4 Months)

• After the initial 2-month phase, treatment should continue with isoniazid and rifampin for an additional 4 months 3, 2
• The continuation phase medications may be administered:
  • Daily (preferred approach) 1
  • Twice weekly under directly observed therapy (DOT) 1
  • Three times weekly under DOT 1

Special Considerations

• For patients with cavitary pulmonary TB who still have positive sputum cultures after 2 months of treatment, the continuation phase should be extended to 7 months (total treatment duration of 9 months) 3, 1
• If drug susceptibility testing confirms that the TB strain is sensitive to both isoniazid and rifampin, ethambutol can be discontinued 1, 2
• For HIV-positive TB patients, treatment should be for a minimum of 9 months and for at least 6 months beyond documented culture conversion 1
• HIV-positive patients with CD4+ counts <100 cells/mm³ should not receive highly intermittent (once or twice weekly) regimens due to risk of rifampin resistance 1, 2

Monitoring During Treatment

• Patients should be medically assessed at least monthly for symptoms and adverse effects 3
• Sputum smear and culture should be obtained at 2 months to assess treatment response 3, 1
• Additional cultures should be obtained monthly until negative 1
• At each monthly visit, patients taking ethambutol should be questioned regarding possible visual disturbances; monthly testing of visual acuity and color discrimination should be performed 3
• Routine measurements of hepatic and renal function are not necessary during treatment unless patients have baseline abnormalities or are at increased risk of hepatotoxicity 3

Directly Observed Therapy (DOT)

• DOT is recommended as the standard of practice to ensure adherence 1, 4
• When using DOT, medications may be given 5 days per week with appropriate dose adjustments 1
• DOT should always be used when medications are administered less than 7 days per week 1
• A major cause of drug-resistant tuberculosis is patient noncompliance with treatment 4

Common Pitfalls and Caveats

• Adding a single drug to a failing regimen can lead to further drug resistance 3, 1
• Treatment failure is often due to patient noncompliance but may also result from ineffective regimens due to drug resistance 1
• If drug resistance is detected, the treatment regimen should be appropriately revised 1, 2
• For patients treated with rifampin who are on methadone, the methadone dosage should be increased to avoid withdrawal symptoms 1
• The decision to stop therapy should be made on the basis of the number of doses taken within a maximum period, not simply a 6-month period 3

Weight-Based Dosing for Pyrazinamide (Adults)

Weight (kg)	40-55	56-75	76-90
Daily, mg (mg/kg)	1,000 (18.2-25.0)	1,500 (20.0-26.8)	2,000 (22.2-26.3)
Thrice weekly, mg (mg/kg)	1,500 (27.3-37.5)	2,500 (33.3-44.6)	3,000 (33.3-39.5)
Twice weekly, mg (mg/kg)	2,000 (36.4-50.0)	3,000 (40.0-53.6)	4,000 (44.4-52.6)

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